Neurokinin 1 receptor and relative abundance of the short and long isoforms in the human brain
Neurokinin 1 receptor and relative abundance of the short and long isoforms in the human brain
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DOI：
10.1046/j.1460-9568.2003.02600.x
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发表时间：
2003-05-01
影响因子：
3.4
通讯作者：
Carletti, R
中科院分区：
文献类型：
--
作者：
Caberlotto, L;Hurd, YL;Carletti, R
P物质主要通过神经激肽-1受体（NK1）相互作用发挥其各种生化作用。最近，NK1受体因其在包括抑郁和焦虑在内的各种精神疾病中的可能作用而引起了相当大的兴趣。然而，关于NK1在人类中枢神经系统（CNS）中的解剖分布知之甚少。进行了核糖探针原位杂交、定量PCR和体外放射自显影。NK1 mRNA水平最高的部位位于蓝斑座和腹侧纹状体，而在大脑皮层（以视觉皮层最丰富）、海马和不同杏仁核中观察到中度杂交信号。在小脑和丘脑中检测到极低水平的NK1 mRNA。鉴于存在NK1受体的长和短同种异构体，评估这两种剪接变体在人类中枢神经系统和外周组织中是否存在差异分布是有意义的。定量TaqMan PCR分析显示，NK1长亚型在整个人脑中最普遍，而在外周组织中，截断型最具代表性。(3) H-Substance P射线自显像显示，受体结合位点与全脑NK1 mRNA表达有良好的相关性，其中蓝斑区结合水平最高。这些结果提供了解剖学上的证据，证明NK1受体与人类大脑中与情绪调节和应激相关的神经系统有很强的关联，但并未表明这两种亚型在中枢神经系统中具有区域特异性作用。
Substance P exerts its various biochemical effects mainly via interactions through neurokinin-1 receptors (NK1). Recently, the NK1 receptor has attracted considerable interest for its possible role in a variety of psychiatric disorders including depression and anxiety. However, little is known regarding the anatomical distribution of NK1 in the human central nervous system (CNS). Riboprobe in situ hybridization, quantitative PCR and in vitro autoradiography were performed. Highest NK1 mRNA levels were localized in the locus coeruleus and ventral striatum, while moderate hybridization signals were observed in the cerebral cortex (most abundant in the visual cortex), hippocampus and different amygdaloid nuclei. Very low levels of the NK1 mRNA were detected in the cerebellum and thalamus. In view of the existence of a long and short isoform of the NK1 receptor, it was of interest to assess whether there was a differential distribution of the two splice variants in the human CNS and peripheral tissues. A quantitative TaqMan PCR analysis showed that the long NK1 isoform was the most prevalent throughout the human brain, while in peripheral tissues the truncated form was the most represented. (3) H-Substance P autoradiography revealed a good correlation between receptor binding sites and NK1 mRNA expression throughout the brain, with the highest levels of binding in the locus coeruleus. These results provide the anatomical evidence that the NK1 receptors have a strong association with neuronal systems relevant to mood regulation and stress in the human brain, but do not suggest a region-specific role of the two isoforms in the CNS.